Taste controls an animals food intake. For the past two decades, our focus has been the isolation and characterization of genes encoding taste receptors and using these to mark the cells, define the corresponding signaling pathways, dissect receptor specificity, generate topographic maps, and trace the respective neuronal connectivity circuits. This research continues to involve a long standing and wide ranging collaboration with Charles Zuker and his groups at Columbia University. Together, we have now established that at the periphery there are 5 distinct classes of taste receptor cells that are selectively tuned to respond to sweet, bitter, sour, sodium salt and savory (umami) tastants and have demonstrated that activation of these cells elicit either appetitive or aversive responses accordingly. Taste information is transmitted to the nucleus of the solitary tract (NST) in the hind-brain through sensory neurons with cell bodies in the geniculate and petrosal ganglia. Projections from the NST diverge: conscious perception of taste quality is thought to involve a pathway that innervates the primary gustatory cortex in the insula; in addition, less well characterized circuits are believed to mediate immediate responses to tastants. Our current work focuses on understanding how taste information is transmitted to the brain and represented there to generate defined percepts and to guide behavior. We are using a battery of modern molecular genetic approaches to define and trace circuits involved and ultimately to relate these circuits to taste perception. These include: Ca-imaging techniques to assess the activity of neural ensembles; screening and sequencing approaches to identify markers for select subsets of taste responsive neuron; and optogenetic, pharmacogenetic, activation and silencing as well as other silencing and ablation approaches to modulate activity of specific parts of the taste circuitry. In this reporting period we have used molecular genetics and functional imaging to probe the mechanisms whereby taste receptor cells (which turn over rapidly) connect to the appropriate neural circuits to drive consistent sensation and behavior. Our results have established a crucial role for distinct semaphorins in establishing appropriate sweet taste receptor to sweet neurons signaling and bitter taste receptor to bitter neuron connectivity.